PROJECT SUMMARY: GENETICALLY ENGINEERED MOUSE FACILITY (GEMF) The MD Anderson Genetically Engineered Mouse Facility (GEMF) provides a wide range of mouse genetic engineering services to investigators at a reasonable cost. Compensated services provided include transgenic mouse generation (using pronuclear and blastocyst injection), gene targeting (using CRISPR/Cas9, transposon-mediated transgenesis, the electroporation of embryonic stem [ES] cells, and TARGATT@ protocols), archiving of mouse embryos and sperm, generation of ES cells from investigators' own mouse lines, and rederivation of mouse lines. In addition, consultation for assessing how genetically engineered animals can contribute to PIs' projects and grant support are provided at no cost. A service unique to the GEMF is the inclusion of a Mouse Resource Facility to provide reagents (e.g., superovulation hormones, ES cell media), DNA plasmids (required for generating DNA constructs for gene targeting and pronuclear injection), and Cre, LacZ, GFP, and p53 transgenic mice (commonly used for the detection and/or generation of conditional mutations in mice and for probing tumor phenotypes). Support provided through CCSG Development Funds was essential for developing the new GEMF service of in vitro transcription of sgRNA. The facility has been in service since 1988 and was started by Dr. Guillermina Lozano, who was appointed director in 2013, and is currently managed by Dr. Jan Parker-Thornburg, the co-director, who is a recipient of an R50 award. The facility has an annual budget of $775,887 (74% for costs for highly expert personnel), $342,039 (44%) of which is supported with CCSG funding. During the present grant period, the institution invested $292,586 in funding for capital equipment, including replacement microscopes, automated injection systems, and a multi-functional electroporation system that can be used both for ES cells and for CRISPR/Cas9 embryo electroporation. Services provided have been fairly evenly distributed among investigators at MD Anderson; 155 cancer center members representing all 16 CCSG programs have used GEMF services over the past 6 years. In grant Yr42, peer-reviewed funding?supported usage accounted for 95% of all usage, and CCSG funds are requested to cover 41% of total expenses in Yr44 ($316,563). The animals and materials produced by the GEMF have contributed significantly to high-impact science at MD Anderson that has resulted in more than 201 publications, including 69 (34%) in journals with IF >10 and 146 (73%) in journals with IF >5. The GEMF's specific aims are: Aim 1. To produce the genetically engineered animal models required by MD Anderson investigators for their studies in cancer research using both traditional and state-of-the-art techniques, based on the need of the faculty. Aim 2. To provide services to MD Anderson investigators to derive and archive mouse models. Aim 3. To use investigator-produced mouse embryos for the generation of unique ES cell lines. Aim 4. To provide expertise and training in the generation, care, and handling of GEM models.